Red blood cells (erythrocytes) are perhaps the most recognizable component of whole blood. Red blood cells contain hemoglobin, a complex iron-containing protein that carries oxygen throughout the body while giving blood its red color. The percentage of blood volume composed of red blood cells is called the “hematocrit”.
The ability to store and preserve red blood cells (RBCs) for later re-infusion into patients is a relatively recent technological development that was the harbinger to modern surgical practice. Such preservation is scientifically tricky and the steps to achieving longer storage duration and higher quality re-infused red blood cells have been incremental. As soon as they are collected from a donor, red blood cells begin to die as they coagulate, starve, lose ATP, 2,3-DPG, membrane surface area and integrity, and hemoglobin (Hb). Acid-citrate-dextrose (ACD), comprising citrate as an anti-coagulant and dextrose as the sole nutrient utilized by red blood cells, and Citrate-phosphate-dextrose solution (CPD), adding phosphate as a metabolic source and for membrane retention, were developed to circumvent this problem. However, whole blood cells kept in CPD and ACD were limited to storage of 21 days.
Almost all of the whole blood collected now is made into components, and the RBC fraction is stored as packed RBCs. For blood drawn into the conservation solution systems, RBCs are packed by centrifugation, plasma is removed so that RBCs make up 80% of the volume, and then conservation solution is added sterilely.
Despite these advances, the concern has been steadily growing over both the national, and worldwide blood supplies. Both the integrity and reliability of existing supplies, and the ability to build larger stocks over time, has been brought into question. One reason for this is the relatively short period of storage stability of blood products. Currently, packed RBCs (red blood cell concentrates, or RCC), the dominant form of blood product for transfusions and the like, are limited to a 42-day storage period.
The gold standard for red cell viability is the survival of 75% of injected radiolabelled cells at 24 h—an arbitrary standard that permits a quarter of transfused erythrocytes to be non-viable. Time-dependent changes in RBC quality and quantity are commonly referred to as the storage lesion. In storage, adenosine triphosphate (ATP) declines with time, resulting in changes in red-cell shape, and decline in membrane lipid content and cell rigidity. Other changes also occur in storage: cells metabolize the glucose in the preservative solution, lactate is produced, pH starts to fall, potassium increases in the suspending medium, free hemoglobin and iron are released from haemolysed red cells, and membrane lipid is shed in the form of vesicles resulting in a diminished function of these cells. Recent evidences suggest that the storage lesion could be responsible for transfusion-associated complications such as immunosuppression and organ failure syndrome.
To circumvent this, compositions were developed to restore volume, nutrients, and other useful RBC stabilizers. These solution compositions for the preservation of red blood cells (RBCs) after their separation from whole blood are intended to be tailored specifically to the needs of RBCs. Example of additive/conservation solution are ACED (citric acid-sodium citrate-dextrose), CPD (citrate-phosphate-dextrose), CPD2, Adsol® (AS-I), Nutricel® (AS-3), Optisol® (AS-5), ErythroSol®, and the like. Typically, these conservations include a carbohydrate, such as glucose or mannitol, at least one phosphate salt, a citrate, and other balancing salts. Red blood cells (RBCs) stored in these solutions, nevertheless, undergo steady deterioration after about 6 weeks as determined by the inability of 75% of such cells to survive in the circulation for 24 hours after re-infusion back into the human donor. It has been observed that during continued refrigerated storage, glucose is consumed at a decreasing rate, as the concentration of metabolic waste, i.e., lactic acid and hydrogen ions, increases. Such a decrease in the rate of glucose metabolism leads to depletion of adenosine triphosphate (ATP), which directly correlates to the recovery of RBCs when the cells are returned to the circulation.
Thus, there is a need for novel RBC storage compositions formulated to improve RBC preservation that results in longer storage duration, reduced storage lesion and/or improved physiological functions of the transfused RBC. Consequently, there remains a need for improved RBC storage compositions and method of manufacture thereof.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.